PROJECT SUMMARY The midbrain superior colliculus (SC) typically requires influence from ipsilateral visual cortex to play its critical role in generating visuomotor responses to contralateral cues. Consequently, visual cortex lesions eliminate both normal visual feature processing and the visual functions of the ipsilateral SC. The result is a contralateral hemianopia. Although insights from animal models suggest amelioration of this deficit is possible through a number of interventions, none of these offers viable therapeutic options for human patients. However we have recently demonstrated that a non-invasive rehabilitative training paradigm (using auditory-visual cues) can permanently reinstate vision in animals rendered hemianopic by unilateral removal of all contiguous areas of visual cortex. Unfortunately, we are largely ignorant of the critical circuitry and experiential antecedents that underly the neural changes that induce this reinstatement of vision., Our preliminary data suggest that cross- modal training produces a functional reorganization in a cortico-SC circuit that involves specific regions of association cortex (i.e., the anterior ectosylvian sulcus, AES). These adaptive changes render SC neurons once again capable of visual responses and of supporting visual behavior in the absence of ipsilateral visual cortex ? presumably via compensatory inputs from AES. Our objective here is to evaluate whether these regions of the AES play an active role in this restructuring during rehabilitative training as well as to determine whether this reorganization is a function of the statistical regularity of cross-modal stimulus presentation. Because we believe that Hebbian mechanisms are able to cause the amplification of typically subthreshold inputs to these regions, rehabilitation occurs as a result of intact and functioning AES regions and high reliability of multimodal stimuli. However, understanding the plasticity of this circuit may allow us to determine in which human patients such therapy would be beneficial as well as how to accelerate the process.